Dapsone is an antibiotic prescribed for acne, pneumonia and leprosy; it’s also an anti-inflammatory. Manueldis 1998 tested it in rats infected intracerebrally with CJD, adminstered orally (in peanut butter) at 2 mg/kg, 6 days per week, starting at 1 day post infection (dpi) and found a 25% delay in symptom onset and 27% extension of survival time (n=4, p<.0001). Guenther 2001 gave mice (infected with ME7 prions via intrahippocampal injection) 8 mg/kg/day in drinking water and found no effect on disease symptoms or any of the many behavioral tests conducted (n and p not stated; and mice were sacrificed at 21 weeks post-infection so there is no ‘survival time’ per se). The only difference Guenther noticed in dapsone-treated scrapie mice compared to untreated scrapie mice was an adverse effect, an exacerbation of the increase in bladder weight that is already associated with scrapie infection. Riemer 2008 used 16.75 mg/kg/day in mice infected intracerebrally with 10-3 brain homogenate of 139A prions, treated with the drug orally in food, starting at 100 dpi, and found no significant difference versus controls (n=9, p > .05).
|citation||animal model||prion strain||infection site||dapsone dose (mouse equivalent)||starting at||treatment onset||control onset||p||n|
|Manueldis 1998||rats||CJD||intracerebral||4 mg/kg*||1 dpi||~380||~310||<.0001||4|
|Guenther 2001||mice||ME7||intrahippocampal microinjection||8 mg/kg||not stated||not stated||not stated||ns|
|Riemer 2008||mice||139A||intracerebral||16.75 mg/kg||100 dpi||189±11.4||unclear||>.05||9|
*See BSA conversion table; rats have Km of 6 compared to mice 3, so 2 mg/kg in rats corresponds to 4 mg/kg in mice.
Manueldis’ original reason for testing dapsone had to do with anti-inflammatory effects and the fact that dapsone “has been used to subdue organisms that hide in macrophages”. Manueldis is the one prion researcher who does not believe in the protein-only hypothesis (her Yale web page implies this is still the case), so the article makes reference to the “infectious agent”. But protein-only believers also found reasons to be interested in dapsone: Riemer notes that other anti-inflammatory agents have been tested in Alzheimer’s with some effect.
As can be seen in the table above, there were many differences in study design between the three studies which could account for the different results. While one study found an effect, dapsone looks to be one of the less promising antiprion drugs reviewed on this blog.